Genetic polymorphism in the conjugating enzyme UGT1A1 and the risk of head and neck cancer

Martin Lacko*, Hennie M. J. Roelofs, Rene H. M. Te Morsche, Adri C. Voogd, Michel B. Oude Ophuis, Wilbert H. M. Peters, Johannes J. Manni

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


UDP-glucuronosyltransferase 1A1 (UGT1A1) is an enzyme which catalyses not only the glucuronidation of tobacco smoke carcinogens like benzopyrene, but also of the endogenous substrate bilirubin. Bilirubin for a long time was considered to be only a toxic waste product of hemoglobin degradation, but recent findings have shown that bilirubin is a potent antioxidant, which may play a protective role against cancer. We investigated whether a genetic polymorphism in UGT1A1 (UGT1A1*28), associated with a reduced UGT1A1 enzyme activity, may have a risk-modifying effect on head and neck carcinogenesis. Blood samples from 421 patients with oral, pharyngeal or laryngeal carcinoma, and 417 healthy controls were investigated for the UGT1A1*28 polymorphism. On the basis of the occurrence of this polymorphism, patients and controls were divided according to predicted UGT1A1 enzyme activity (low, intermediate, high). Logistic regression analysis showed a significant increased distribution of predicted high activity UGT1A1*1 polymorphisms among the patients (OR: 1.37; 95% CI: 1.02-1.83). Stratified analyses demonstrated that predicted high activity UGT1A1 polymorphisms were present even more significantly in patients with laryngeal cancer, older patients, heavy smokers and heavy drinkers. In conclusion, the predicted high activity UGT1A1*1 polymorphism, which results in lower serum levels of the endogenous antioxidant bilirubin, was associated with an increased risk of head and neck cancer.
Original languageEnglish
Pages (from-to)2815-2821
JournalInternational Journal of Cancer
Issue number12
Publication statusPublished - 15 Dec 2010


  • head and neck carcinoma
  • UDP-glucuronosyltransferase 1A1
  • genetic polymorphism
  • carcinogenesis
  • bilirubin


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